Cassel's breakthrough role was in Mathieu Kassovitz's critically acclaimed film La Haine where he played a troubled youth from the deprived outskirts of Paris. He has gone on to act in a variety of films such as the moody L'Appartement (with Monica Bellucci before they married),[3] the violent Dobermann, the genre-bending Le Pacte des Loups (in English, Brotherhood of the Wolf), and the highly controversial Irréversible, where he appears fully nude (with Monica Bellucci after they married).

In October 2008, Cassel was signed to be the face of a new Yves Saint Laurent men's fragrance. The new fragrance, La Nuit de l'Homme, was launched worldwide in March 2009.

French film historian Tim Palmer describes Cassel as one of the most charismatic and idiosyncratic of all France's contemporary stars, working in both popular and more intellectual modes of cinema, typically playing characters that veer unpredictably between positive/alluring and negative/grotesque—often, in fact, within a single role and performance.[5]

In 2009, he made his debut as a singer on Zap Mama's album ReCreation, singing alongside them on the singles "Paroles, Paroles" and "Non, Non, Non".

Cassel met Italian actress Monica Bellucci on the set of their 1996 film The Apartment.[6] They married in 1999,[6] and have two daughters, Deva (born 12 September 2004)[7] and Léonie (born 21 May 2010).[8] Cassel and Bellucci announced their separation in August 2013.[6]